Abstract This novel prospective cohort study will explore the relationship between kidney transplantation (antibiotics, antivirals, and immunosuppressants), changes in the composition and functional gene content of the microbiome, and the incidence and severity of patient reported symptoms before and after patients receive a kidney transplant from a live donor. We have selected living donor recipients to reduce the chance of missing samples, as these are scheduled surgeries. Thirty-nine subjects will provide stool and sputum samples for shot gun metagenomic sequencing of the microbiome before transplant, during the first week after transplant prior to discharge, and at 3 months after the transplant. Demographic (age, gender, race/ethnicity, income, education) and disease specific data (HT/WT/BMI, creatinine, estimated glomerular filtration rate, basic metabolic panel, complete blood count), and medication adherence data (electronic medication adherence monitoring and tacrolimus trough levels) will be collected. Potential confounding variables will include: historical use of antibiotics, concomitant medications, mode of delivery (vaginal vs. caesarian birth), and nutritional status (Diet History Questionnaire III). Incidence and severity of symptoms of fatigue, sleep dysfunction, and anxiety/depression?like symptoms will be measured using the Patient Reported Outcome Measurement Systems (PROMIS) 57 v2.1. Health related quality of life will be assessed using the Kidney Disease Quality of Life Short Form (KDQOL-SF v1.3). This research will support the mission of the National Institute of Nursing Research (NINR) to promote and improve the health and quality of life of individuals, families, and communities. The proposed study will contribute to the NINR mission by: 1) Exploring the mechanisms underlying incidence and severity of symptoms after kidney transplantation with the goal of developing personalized treatments, including pre-probiotics supplementation, lifestyle modification, and dietary interventions that address these mechanisms through symptom science research; 2) Helping individuals with chronic kidney disease/kidney transplant recipients better understand and manage these conditions by engaging individuals as active participants in managing their own health through awareness of modifiable factors that alter the microbiome; and 3) Promoting the development of innovative, multidisciplinary, nurse-led teams to advance research on microbiome and health after kidney transplantation.